Fatty acid transport proteins (FATP) are membrane-bound proteins that transport free fatty acids (FFA) across the plasma membrane, and are thus responsible for cellular uptake of FFA from the extracellular space. Chiu et al., report that transgenic overexpression of FATP1 in the heart leads to increased lipid uptake, lipotoxicity, and cardiac myopathy (Circ. Res., 96:225-233, 2005). Chiu et al. illustrate the critical need for a controlled uptake of FFA to tissues. Accumulated FFA are not properly oxidized can be toxic to cells.
Lipid accumulation in tissues, particularly of skeletal muscle, has also been suggested to induce insulin resistance syndrome (also know as the diabetic metabolic syndrome). FATP4 has been shown by linkage analysis to be a candidate gene in the insulin resistance syndrome characterized by dyslipidemia, hypertension, and the procoagulant state (Gertow et al., Clin. Endocrinol. Metab., 89:392-399, 2004, the disclosure of which is incorporated herein by reference). Similarly, FATP1 has been linked with elevated post-prandial lipaemia and alterations in LDL particle size distribution Gertow et al., Atherscler., 167:265-273, 2003, the disclosure of which is incorporated herein by reference). A review of fatty acid transport proteins and their role in insulin resistance can be found in Fisher et Ed., Curr. Opin. Lipidol., 16:173-178, 2005, the disclosure of which is incorporated herein by reference.
Aberrant lipid accumulation is closely related to deleterious lipotoxic effects, insulin resistance, perturbations of both lipid and carbohydrate metabolism and other features of the metabolic syndrome (Unger et al., Endocrinol., 144:5159-5164, 2004, the disclosure of which is incorporated herein by reference). Thus, a need exists for new materials and methods for modulating FATP expression and/or activity in vivo, for prophylaxis or therapy of various diseases and conditions that are influenced by FATPs.